Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths) in 2008. Ovarian cancer is the ninth most common cancer in women and the fifth leading cause of cancer-related deaths in women in the US. One of every 72 women will develop ovarian cancer and one of every 100 will die from this form of cancer. The American Cancer Society estimates that in 2013, 22,240 women will be diagnosed with ovarian cancer and about 14,230 will die from ovarian cancer. About 85% to 90% of ovarian cancers are epithelial ovarian carcinomas.
Treatment options include surgery, chemotherapy, and occasionally radiation therapy. Surgery usually involves the removal of one or both ovaries, fallopian tubes and the uterus. In advanced disease, surgically removing all abdominal metastases enhances the effect of chemotherapy and helps improve survival. For women with stage III ovarian cancer in which removal of cancerous tissue has been performed, studies show that chemotherapy administered both intravenously and directly into the peritoneal cavity improves survival.
The identification of tumor markers suitable for early detection and diagnosis of cancer and in particular, ovarian cancer would improve the clinical outcome of patients, especially those presenting vague or no symptoms. Presently no cost effective screening tests have been developed.
Ovarian epithelial cancer is more common in individuals with elevated gonadotropin-releasing hormone (GnRH) including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), such as postmenopausal women or women who have received treatment to induce ovulation. Conversely, reduced risk of ovarian cancer is associated with a history of multiple pregnancies, breastfeeding, oral contraceptive use, and estrogen replacement therapy, all of which are related to lower levels of and reduced exposure to FSH and LH. FSH, follicle stimulating hormone, regulates gene expression in ovarian tumors (Chu S, Rushdi S, Zumpe E T, Mamers P, Healy D L, Jobling T, Burger H G, Fuller P J. (2002) FSH-regulated gene expression profiles in ovarian tumors and normal ovaries. Mol Hum Reprod. 8:426-33) and causes neovascularization of ovarian cancers by increasing vascular endothelial growth factor (VEGF) expression through upregulation of surviving (Huang Y, Hua K, Zhou X, Jin H, Chen X, Lu X, Yu Y, Zha X, Feng Y. (2008) Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma. Cell Res. 18:780-91).
Currently, cancer antigen 125 (CA-125) is used as a serum biomarker for ovarian cancer. Serum concentrations of CA-125 are elevated in 75-80% of patients with advanced-stage disease and this marker. CA125 is used as a serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, as well as distinguishing malignant from benign pelvic masses. However, it is presently not an appropriate diagnostic biomarker as the majority of healthy women with high levels of CA-125 do not have cancer.
Accordingly, there is a need for improved methods of detection and diagnosis of cancer including ovarian cancer as well as methods for monitoring the progress of the disease and monitoring the progress of various treatments for ovarian cancer including point of care or point of use devices capable of quantitating predictive biomarker(s).